Journal of Pain Research (Jul 2023)
Methylnaltrexone Treatment for Opioid-Induced Constipation in Patients with and without Cancer: Effect of Initial Dose
Abstract
Bruce H Chamberlain,1 Michelle Rhiner,2 Neal E Slatkin,3,4 Nancy Stambler,5 Robert J Israel6 1Genesis Healthcare, Davenport, IA, USA; 2Department of Family Medicine, Loma Linda University Health, Loma Linda, CA, USA; 3University of California Riverside, School of Medicine, Riverside, CA, USA; 4Salix Pharmaceuticals, Medical Affairs, Bridgewater, NJ, USA; 5Progenics Pharmaceuticals, Inc, a subsidiary of Lantheus Holdings, Inc, Clinical Research, North Billerica, MA, USA; 6Bausch Health US, LLC, Clinical and Medical Affairs, Bridgewater, NJ, USACorrespondence: Robert J Israel, Bausch Health US, LLC, Clinical and Medical Affairs, 400 Somerset Corporate Boulevard, Room 6-1001, Bridgewater, NJ, 08807, USA, Tel +1 908 541-2288, Fax +1 585 338-0668, Email [email protected]: Opioid-induced constipation (OIC) is a common side effect of opioid therapy. Methylnaltrexone (MNTX) is a selective, peripherally acting μ-opioid receptor antagonist, with demonstrated efficacy in treating OIC. We pooled results from MNTX clinical trials to compare responses to an initial dose in patients with chronic cancer and noncancer pain.Patients and Methods: This post hoc analysis used pooled data from 3 randomized, placebo-controlled studies of MNTX in patients with advanced illness with OIC. Assessments included the proportions of patients achieving rescue-free laxation (RFL) within 4 and 24 hours of the first study drug dose, time to RFL, current and worst pain intensity, and adverse events, stratified by the presence/absence of cancer.Results: A total of 355 patients with cancer (MNTX n = 198, placebo n = 157) and 163 without active cancer (MNTX n = 83; placebo n = 80) were included. More patients treated with MNTX compared with those who received placebo achieved an RFL within 4 (cancer: MNTX, 61.1% vs placebo,15.3%, p< 0.0001; noncancer: MNTX, 62.2% vs placebo, 17.5%, p< 0.0001) and 24 hours (cancer: MNTX, 71.2% vs placebo, 41.4%, p< 0.0001; noncancer: MNTX, 74.4% vs placebo, 37.5%, p< 0.0001) of the initial dose. Cumulative RFL response rates within 4 hours of the first, second, or third dose of study drug were also higher in MNTX-treated patients. The estimated time to RFL was shorter among those who received MNTX and similar in cancer and noncancer patients. Mean pain scores declined similarly in all groups. The most common adverse events in both cancer and noncancer patients were abdominal pain, flatulence, and nausea.Conclusion: After the first dose, MNTX rapidly induced a laxation response in the majority of both cancer and noncancer patients with advanced illness. Opioid-induced analgesia was not compromised, and adverse events were primarily gastrointestinal in nature. Methylnaltrexone is a well-tolerated and effective treatment for OIC in both cancer and noncancer patients.Keywords: peripheral mu-opioid receptor antagonist, PAMORA, chronic pain, opioid
